Comparison of the effects of NS-21 and terodiline on the QTc interval in dogs.
1. NS-21 [(+/-)-4-diethylamino-1,1-dimethylbut-2-yn-1-yl 2-cyclohexyl-2-hydroxy-2-phenylacetate monohydrochloride monohydrate], its active metabolite, RCC-36, and terodiline, are mixed anticholinergic-Ca2+ antagonistic drugs. Among them, terodiline has been shown to cause torsade de pointes, a serious polymorphic ventricular tachycardia. It remains unknown, however, whether NS-21 or its active metabolite, RCC-36, produces torsade de pointes. 2. In anesthetized dogs, terodiline (10 mg/kg i.v.) significantly prolonged the QTc interval by 6-8%, an effect thought to be associated with torsade de pointes. In contrast, neither NS-21 nor RCC-36 (10 mg/kg i.v.) prolonged the QTc interval; therefore NS-21 is unlikely to cause ventricular tachyarrhythmias, such as those associated with terodiline. 3. The effects of NS-21, RCC-36 and terodiline on the action potential were investigated in guinea pig papillary muscle. However, none of these drugs prolonged the duration of the action potential, although only terodiline caused the muscle preparation to lose its excitability.
Natsukawa
T
T
Research Laboratories, Nippon Shinyaku Co., Ltd., Kyoto, Japan.
Matsuzaki
T
T
Hayashi
S
S
Ukai
Y
Y
Yoshikuni
Y
Y
Kimura
K
K
D000818:Animals; D002082:Butylamines / Q000493:pharmacokinetics / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000493:pharmacokinetics / Q000494:pharmacology*; D018680:Cholinergic Antagonists / Q000494:pharmacology*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography / Q000187:drug effects*; D004594:Electrophysiology; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D010648:Phenylacetates / Q000493:pharmacokinetics / Q000494:pharmacology*
D002082:Butylamines; D002121:Calcium Channel Blockers; D018680:Cholinergic Antagonists; D010648:Phenylacetates; C107100:RCC 36; C010637:terodiline; C105354:temiverine